LC1 – Liver Cancer

1. Oldenlandia diffusa and Scutellaria barbata augment macrophage oxidative burst and inhibit tumor growth.
Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumors. In this study we determined the effects of these phytochemicals on oxidative burst as an indicator of phagocytic function in a murine macrophage cell line J774 using an automated micro-fluorometric assay. A dose-dependent augmentation of oxidative burst was observed with OD as well as SB. The effect of OD and SB on the growth of a murine renal cell carcinoma (Renca) was also determined. Balb/c mice were transplanted subcutaneously with 1´10(5) Renca cells and were randomized into groups of 10 to receive oral feeding of OD (4 mg/day), SB (4 mg/day), or saline as control. Oral feeding with either OD or SB significantly inhibited the growth of Renca in mice. The data of this study show that OD and SB are capable of enhancing macrophage function in vitro and inhibiting tumor growth in vivo.
––Wong BY, Lau BH, Jia TY, Wan CP. Cancer Biother Radiopharm 1996 Feb;11(1):51-6.

2. Chinese medicinal herbs modulate mutagenesis, DNA binding and metabolism of aflatoxin B1.
Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumors while Astragalus membranaceus (AM) and Ligustrum lucidum (LL) are often used as an adjunct in cancer therapy. In this study, we determined the effects of aqueous extracts of these four herbs on aflatoxin B1 (AFB1)-induced mutagenesis using Salmonella typhimurium TA100 as the bacterial tester strain and rat liver 9000 x g supernatant as the activation system. The effects of these herbs on [3H]AFB1 binding to calf-thymus DNA were assessed. Organosoluble and water-soluble metabolites of AFB1 were extracted and analyzed by high-performance liquid chromatography (HPLC). Mutagenesis assays revealed that all of these herbs produced a concentration-dependent inhibition of histidine-independent revertant (His+) colonies induced by AFB1. At a concentration of 1.5 mg/plate, SB and OD in combination exhibited an additive effect. The trend of inhibition of these four herbs on AFB1-induced mutagenesis was: SB greater than LL greater than AM. LL, OD and SB significantly inhibited AFB1 binding to DNA, reduced AFB1-DNA adduct formation, and also significantly decreased the formation of organosoluble metabolites of AFB1. Our data suggest that these Chinese medicinal herbs possess cancer chemopreventive properties.
––Wong BY, Lau BH, Tadi PP, Teel RW.  Mutat Res 1992 Jun 1;279(3):209-16.

1. Experimental study on effect of Angelica polysaccharide in inhibitory proliferation and inducing differentiation of K562 cells
OBJECTIVE: To investigate the application value of Angelica polysaccharide (APS) on proliferation and differentiation of human erythroleukemia K562 cells. METHODS: The effect of APS in inhibitory proliferation and inducing differentiation of human erythroleukemia K562 cells was studied by modern experimental hematologic techniques such as cell counting and culture, flowcytometry, morphology, cytochemistry and cell differential immune phenotyping. RESULTS: APS could significantly inhibit the proliferation of K562 cells in vitro and prevent the cell from entering the active proliferative phase (P < 0.05). After being induced by APS, the differentiation of K562 cells to erythrocyte series and granulo-monocyte series increased, positive rate of benzidine, glycogen and peroxidase stain elevated, and cell surface differential antigen CD15 expression promoted significantly (P < 0.05), while C-MYC expression of K562 cells induced by APS induction lowered significantly (P < 0.05). CONCLUSION: APS could not only inhibit the proliferation of K562 cells in vitro, but also induce the differentiation of K562 cells toward erythrocyte and granulocyte series. It may be a natural inducer with promising prospect of development and application.
––Zheng M, Wang YP. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002 Jan;22(1):54-7.  

2. Immunopharmacological studies of low molecular weight polysaccharide from Angelica sinensis.
A low molecular weight polysaccharide has been isolated from the rhizome of Angelica sinensis (Oliv.) Diels (Umbelliferaer). It has a molecular weight of approximately 3,000 and consists of protein (4.73%) and carbohydrate (85.85%) of which 5.2% is uronic acid. It shows strong anti-tumor activity on Ehrlich Ascites tumor bearing mice. It also exhibits immunostimulating activities, both in vitro and in vivo.
––Choy YM, Leung KN, Cho CS, Wong CK, Pang PK. Am J Chin Med. 1994;22(2):137-45.

3. Clinical Studay
Hua Liu Tang: dang gui wei, 10g; chi shao, 10g; hong hua 10g; tao ren 10g; dan shen 20g; shu zhi 10g; ban zhi lian 30g; bai hua she she cao 30g, 5 cases of brain tumor were treated for 6 months, and they survived for 2~7 years. Among 28 cases of thyrophyma, all were effective except for 3 cases.

1. Inhibition of tumor growth by S-3-1, a synthetic intermediate of salvianolic acid A.
Salvianolic acid A (1) is one of the active components from Salvia miltiorrhiza, which was found to suppress the growth of mouse tumors. S-3-1 (a 2-allyl-3,4-dihydroxybenzaldehyde, 2) is a synthetic intermediate of a salvianolic acid A derivative with strong inhibitory effects on the growth of cancer cells in vitro. The inhibitory effects of 2 on tumor growth and its molecular targets were studied. 2 significantly suppressed the growth of mouse Lewis lung carcinoma, S180 sarcoma and H22 hepatic carcinoma in a dose-dependent manner. With a simple scrape-loading dye transfer method, 20 microg/ml of 2 was found to significantly enhance gap junction intercellular communication (GJIC) in human pancreatic adenocarcinoma PaCa Cells, human lung epithelial carcinoma W1-38 cells and human lung adenocarcinoma A549 cells, but 2 had no marked effect on GJIC in human colon cancer CACO2 cells. With Northern blot analysis, 2 was found to inhibit the expression of c-myc gene in A549 cells and have no marked effect on H-ras oncogene expression, and increase the cellular P53 mRNA contents, though it did not affect the expression of RB tumor suppressor gene. 2 also suppressed the P46 (JNK/SAPK) expression in A549 cells. Western blot analysis was applied to visualize the P21ras protein. Results shows that 2 at concentrations ranging from 10 to 20 microg/ml decreases the contents of the membranous P21ras and total P21ras and increases the contents of cytosolic P21ras protein in a time-dependent manner. However, 2 had no significant effects on farnesyl protein transferase activities at the concentrations that could efficiently decrease the membranous P21ras content. This suggested that 2 might suppress tumor growth partly through enhancement of GJIC and reversion of the transformed phenotypes. The other mechanisms may be that 2 can suppress the overexpression of c-myconcogene, inhibit the function of Ras oncoprotein, increase the expression of P53 tumor suppressor gene and interrupt P46-associated mitogen-activated pathway other than farnesylation of Ras protein.
––Li HY, Li Y, Yan CH, Li LN, Chen XG. J Asian Nat Prod Res. 2002 Dec;4(4):271-80. 

2. Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG(2) cells.
Salvia miltiorrhiza (SM) is a traditional Chinese herbal medicine, commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that SM exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we evaluated the molecular mechanism of SM in a human hepatoma cell line, HepG(2). Our results show that SM exerted clear cytotoxic effects, and strongly inhibited the proliferation of HepG(2) cells. It was also observed that SM treatment caused apoptotic cell death as evaluated by: (a), morphological changes by using acridine orange/ethidium bromide staining; (b), DNA fragmentation by TdT-mediated dUTP nick end labeling (TUNEL); and (c), sub-G(1) cell analysis. Furthermore, depletion of intracellular glutathione (GSH) and reduction of mitochondrial membrane potential were found to be involved in the initiation of apoptosis by SM.
––Liu J, Shen HM, Ong CN. Cancer Lett. 2000 May 29;153(1-2):85-93. 

1. Inhibitory effect of alkane-6,8-diols, the components of safflower, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.
Erythro-alkane-6,8-diols were isolated from the flowers of Carthamus tinctorius. 12-0-Tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear), a tumor-promoting agent, was applied to the ears of mice to induce inflammation. Of 8 alkane-6,8-diols assayed, the C27, C31, C32, C33 and C35 alkane diols inhibited the inflammation. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.5-0.7 mg/ear. However, C21, C23 and C25 alkane-6,8-diols were found to have no effect. Furthermore, the mixture of erythro-alkane-6,8-diols from the flowers of C. tinctorius markedly suppressed the promoting effect of TPA on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene.
––Yasukawa K, Akihisa T, Kasahara Y, Kaminaga T, Kanno H, Kumaki K, Tamura T, Takido M. Oncology. 1996 Mar-Apr;53(2):133-6. 

1. Anticancer effect
Polyphenolic substance obtained from bing lang had obvious inhibitory effect on Ehrlich carcinoma, it had medium cytoxic effect on Hela cells.

2. Inhibitory effect of bupleuri radix saponins on adhesion of some solid tumor cells and relation to hemolytic action: screening of 232 herbal drugs for anti-cell adhesion.
Among 232 herbal drugs tested, six showed a remarkable anti-cell adhesive activity, and the extract from the roots of Bupleurum falcatum (Umbelliferae), the semen of Psorala corylifolia (Leguminosae), and the semen of Areca catechu (Palmae) showed an anti-cell adhesive action at non-cytotoxic concentrations. Saikosaponins-a, d and e, isolated from the roots of Bupleurum falcatum, exhibited a potent anti-cell adhesive activity and a strong hemolytic action. In a structure-activity relationship for both activities, it seems that a sugar moiety and an ether linkage between C-13 and C-28 are required for good bioactivities. In addition, saikosaponin d with a beta-hydroxy group at C-16 was more potent than saikosaponin a possessing an alpha-hydroxy group. Taken together, it is suggested that the mechanism for anti-cell adhesive activity of saikosaponin may resemble that for their hemolytic action.
––Ahn BZ, Yoon YD, Lee YH, Kim BH, Sok DE. Planta Med. 1998 Apr;64(3):220-4. 

No related research.

1. Interventional therapy combining Seed of Job's-tears with lipiodol for hepatoma-bearing rats
OBJECTIVE: To study the effect of the interventional therapy of hepatoma-bearing rat by Seed of Job's-tears (SJT) injection combining with lipiodol. METHODS: To evaluate the effect of SJT as a medicament which can be used in interventional therapy, we repeated the hepatoma-bearing rats, and treated them by interventional therapy with SJT referring to the method which Lindel set up, comparing its effect to which of chemical medicines and lipiodol. RESULTS: SJT or lipiodol alone had an inhibiting effect to liver cancer. The tumor growth rates were 13.89%, 14.05%, and the tumor inhibiting rates reached 38.10%, 37.49%. The curative effect of the SJT/lipiodol group was the best, and its growth rate and inhibiting rate were 3.36% and 85.03%, respectively better than the SJT group and lipiodol group (P<0.01). There was no statistically significant difference between the effect of the SJT/lipiodol group and the mitomycin/lipiodol group. The survival period of SJT/lipiodol group was longer than the rest groups (P<0.01 or P<0.05). CONCLUSIONS: The interventional therapy by SJT/lipiodol has obvious inhibitory effect on the growth of hepatoma-bearing rats, which is similar to that of MMC/lipiodol. This inhibiting effect is better than that of the SJT or lipiodol group. SJT/lipiodol can prolong the survival period of hepatoma-bearing rats obviously, and this effect is better than that of single lipiodol, SJT or MMC/lipiodol.
––Huang T, Wu W, Li Y, Zhang J, Huang L. Zhonghua Gan Zang Bing Za Zhi. 2002 Dec;10(6):452-4. 

2. Anticancer effect
Intraperitoneal injection of ethanol extract of yi yi ren had inhibitory effect on Ehrlich carcinoma of mice, and could lengthen the survival time of animals. Acetone extract of yi yi ren had obvious inhibitory effect on mice cervical cancer-14 (U-14) and HCA solid tumor.

3. Clinical study
Yi Yi Ren Syrup (100ml was equal to 50g crude drug), oral administration, 20~40ml, 3 times daily. It was used to treat lung cancer , intestinal cancer, stomach cancer, cervical cancer, etc.. yi yi ren ombined with teng liu, he zi an ling jiao was used to treat alimentary tract cancers. 168 cases of patients were treated, 1 dose every day, taken in three times. After treatment, the appetite and general condition were improved. And this formula had certain therapeutic effects on 30 cases out of 36 cases who took over three months’ treatment.

No related research.

1. Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway.
Paeoniae Radix (PR) is the root of traditional Chinese Herb named Paeonia lactiflora Pallas, which is commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that PR has anticancer growth activities, however the mechanism underlying these activities was unclear and remained to be elucidated. In this study, we evaluated the molecular mechanism of the effect of PR on human hepatoma cell lines, HepG2 and Hep3B. Our results showed that the water-extract of Paeoniae Radix (PRE) had inhibitory effect on the growth of both HepG2 and Hep3B cell lines. The induction of internucleosomal DNA fragmentation and chromatin condensation appearance, and accumulation of sub-G1 phase of cell cycle profile in PRE treated hepatoma cells evidenced that the cytotoxicity of PRE to the hepatoma cells is through activation of the cell death program, apoptosis. The activation of apoptosis by PRE is independent of the p53 pathway as Hep3B cell is p53-deficient. In addition, the differential gene expression of PRE treated HepG2 was examined by cDNA microarray technology and RT-PCR analysis. We found that the gene expression of BNIP3 was up-regulated while ZK1, RAD23B, and HSPD1 were down-regulated during early apoptosis of the hepatoma cell mediated by PRE. The elucidation of the drug targets of PR on inhibition of tumor cells growth should enable further development of PR for liver cancer therapy.
––Lee SM, Li ML, Tse YC, Leung SC, Lee MM, Tsui SK, Fung KP, Lee CY, Waye MM. Life Sci. 2002 Sep 27;71(19):2267-77. 

2. Pharmacotherapeutic effects of kuei-chih-fu-ling-wan (keishi-bukuryo-gan) on human uterine myomas.
Kuei-chih-fu-ling-wan (Keishi-bukuryo-gan; KBG), a traditional Chinese herbal remedy (Gui Zhi Fu Ling Wan) contains five components: bark of Cinnamomum cassia Bl. (Lauraceae), root of Paeonia lactiflora Pall. (Paeoniaceae), seed of Prunus persica Batsch. or P. persiba Batsch.var.davidiana Maxim. (Rosaceae), carpophores of Poria cocos Wolf. (Polyporaceae), and root bark of Paeonia suffruticosa Andr. (Paeoniaceae). This prescription has been frequently used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and sterility. We previously reported that KBG might act as a LH-RH antagonist and a weak anti-estrogen on the uterine DNA synthesis in immature rats. In the present study, we investigated the effects of KBG on 110 premenopausal patients with uterine myomas. Clinical symptoms of hypermenorrhea and dysmenorrhea were improved in more than 90% of the cases with shrinking of uterine myomas in roughly 60% of the cases.
––Sakamoto S, Yoshino H, Shirahata Y, Shimodairo K, Okamoto R. Am J Chin Med. 1992;20(3-4):313-7.